{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:17:31Z","timestamp":1775585851996,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["DST\/SEED\/SUTRA\/2020\/284"],"award-info":[{"award-number":["DST\/SEED\/SUTRA\/2020\/284"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The leaves of <jats:italic>Araucaria cunninghamii<\/jats:italic> are known to be nonedible and toxic. Previous studies have identified biflavones in various <jats:italic>Araucaria<\/jats:italic> species. This study aimed to investigate the in\u00a0vitro cytotoxicity of the isolated compounds from <jats:italic>Araucaria cunninghamii<\/jats:italic> after metabolomics and network pharmacological analysis. Methanol extract of <jats:italic>Araucaria cunninghamii<\/jats:italic> leaves was subjected to bioassay\u2010guided fractionation. The active fraction was analyzed using LC\u2010HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta\u2010sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound\u2010gene\u2010pathway network and hierarchical network analysis, protein\u2013protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC<jats:sub>50<\/jats:sub> 90.58\u2009\u03bcM) exhibits the highest cytotoxicity and monomeric apigenin (IC<jats:sub>50<\/jats:sub> 174.5\u2009\u03bcM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy \u2264\u22127 Kcal\/mol.<\/jats:p>","DOI":"10.1111\/cbdd.14564","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T08:21:26Z","timestamp":1717748486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the cytotoxic potential of biflavones of <i>Araucaria\u00a0cunninghamii<\/i>: Precise identification combined by LC\u2010HRMS\u2010metabolomics and database mining, targeted isolation, network pharmacology, in\u00a0vitro cytotoxicity, and docking studies"],"prefix":"10.1111","volume":"103","author":[{"given":"Bharat","family":"Sahu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering and Technology Indian Institute of Technology (B.H.U)  Varanasi 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Engineering Indian Institute of Technology Indore  Indore Madhya Pradesh India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6160-8755","authenticated-orcid":false,"given":"Shreyans K.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering and Technology Indian Institute of Technology (B.H.U)  Varanasi 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